OBJECTIVE Several studies reported gender differences in aldosterone. It is unknown whether these differences are associated with differences in volume regulation. Therefore, we studied both aldosterone and extracellular volume in men and women on different sodium intakes. METHODS In healthy normotensive men (n=18) and premenopausal women (n=18) we investigated plasma aldosterone, blood pressure, and extracellular volume (125I-iothalamate), during both a low (target intake 50 mmol Na+/day) and high sodium intake (target intake 200 mmol Na+/day) in a cross-over set-up. Furthermore, we studied the adrenal response to angiotensin II infusion (0.3, 1.0 and 3.0 ng/kg/min for 1 h) on both sodium intakes. RESULTS Men had a significantly higher plasma aldosterone, extracellular volume and systolic blood pressure than women during a high sodium intake (p<0.05). During a low sodium intake, extracellular volume and blood pressure were higher in men as well (p<0.05), whereas the difference in plasma aldosterone was no longer significant (P=0.252). The adrenal response to exogenous angiotensin II was significantly lower in men than in women on both sodium intakes. CONCLUSIONS Constitutive gender differences in the regulation of aldosterone, characterized by a higher aldosterone and a lower adrenal response to exogenous angiotensin II infusion in men, are associated with a higher extracellular volume and blood pressure in men. These findings suggest that gender differences in the regulation of aldosterone contribute to differences in volume regulation between men and women.